1c0g
From Proteopedia
(New page: 200px<br /> <applet load="1c0g" size="450" color="white" frame="true" align="right" spinBox="true" caption="1c0g, resolution 2.00Å" /> '''CRYSTAL STRUCTURE O...) |
|||
| Line 1: | Line 1: | ||
| - | [[Image:1c0g.gif|left|200px]]<br /> | + | [[Image:1c0g.gif|left|200px]]<br /><applet load="1c0g" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1c0g" size=" | + | |
caption="1c0g, resolution 2.00Å" /> | caption="1c0g, resolution 2.00Å" /> | ||
'''CRYSTAL STRUCTURE OF 1:1 COMPLEX BETWEEN GELSOLIN SEGMENT 1 AND A DICTYOSTELIUM/TETRAHYMENA CHIMERA ACTIN (MUTANT 228: Q228K/T229A/A230Y/E360H)'''<br /> | '''CRYSTAL STRUCTURE OF 1:1 COMPLEX BETWEEN GELSOLIN SEGMENT 1 AND A DICTYOSTELIUM/TETRAHYMENA CHIMERA ACTIN (MUTANT 228: Q228K/T229A/A230Y/E360H)'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Replacement of residues 228-230 or 228-232 of subdomain 4 in Dictyostelium | + | Replacement of residues 228-230 or 228-232 of subdomain 4 in Dictyostelium actin with the corresponding Tetrahymena sequence (QTA to KAY replacement: half chimera-1; QTAAS to KAYKE replacement: full chimera) leads to a higher Ca(2+)-activation of the regulated acto-myosin subfragment-1 ATPase activity. The ratio of ATPase activation in the presence of tropomyosin-troponin and Ca(2+) to that without tropomyosin-troponin becomes about four times as large as the ratio for the wild-type actin. To understand the structural basis of this higher Ca(2+)-activation, we have determined the crystal structures of the 1:1 complex of Dictyostelium mutant actins (half chimera-1 and full chimera) with gelsolin segment-1 to 2.0 A and 2.4 A resolution, respectively, together with the structure of wild-type actin as a control. Although there were local changes on the surface of the subdomain 4 and the phenolic side-chain of Tyr230 displaced the side-chain of Leu236 from a non-polar pocket to a more solvent-accessible position, the structures of the actin chimeras showed that the mutations in the 228-232 region did not introduce large changes in the overall actin structure. This suggests that residues near position 230 formed part of the tropomyosin binding site on actin in actively contracting muscle. The higher Ca(2+)-activation observed with A230Y-containing mutants can be understood in terms of a three-state model for thin filament regulation in which, in the presence of both Ca(2+) and myosin heads, the local changes of actin generated by the mutation (especially its phenolic side-chain) facilitate the transition of thin filaments from a "closed" state to an "open" state. Between 394 and 469 water molecules were identified in the different structures and it was found that actin recognizes hydrated forms of the adenine base and the Ca ion in the nucleotide binding site. |
==Disease== | ==Disease== | ||
| Line 11: | Line 10: | ||
==About this Structure== | ==About this Structure== | ||
| - | 1C0G is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Dictyostelium_discoideum_and_tetrahymena_thermophila Dictyostelium discoideum and tetrahymena thermophila] and [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with CA and ATP as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 1C0G is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Dictyostelium_discoideum_and_tetrahymena_thermophila Dictyostelium discoideum and tetrahymena thermophila] and [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=CA:'>CA</scene> and <scene name='pdbligand=ATP:'>ATP</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1C0G OCA]. |
==Reference== | ==Reference== | ||
| Line 30: | Line 29: | ||
[[Category: contractile protein]] | [[Category: contractile protein]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:01:10 2008'' |
Revision as of 10:01, 21 February 2008
|
CRYSTAL STRUCTURE OF 1:1 COMPLEX BETWEEN GELSOLIN SEGMENT 1 AND A DICTYOSTELIUM/TETRAHYMENA CHIMERA ACTIN (MUTANT 228: Q228K/T229A/A230Y/E360H)
Contents |
Overview
Replacement of residues 228-230 or 228-232 of subdomain 4 in Dictyostelium actin with the corresponding Tetrahymena sequence (QTA to KAY replacement: half chimera-1; QTAAS to KAYKE replacement: full chimera) leads to a higher Ca(2+)-activation of the regulated acto-myosin subfragment-1 ATPase activity. The ratio of ATPase activation in the presence of tropomyosin-troponin and Ca(2+) to that without tropomyosin-troponin becomes about four times as large as the ratio for the wild-type actin. To understand the structural basis of this higher Ca(2+)-activation, we have determined the crystal structures of the 1:1 complex of Dictyostelium mutant actins (half chimera-1 and full chimera) with gelsolin segment-1 to 2.0 A and 2.4 A resolution, respectively, together with the structure of wild-type actin as a control. Although there were local changes on the surface of the subdomain 4 and the phenolic side-chain of Tyr230 displaced the side-chain of Leu236 from a non-polar pocket to a more solvent-accessible position, the structures of the actin chimeras showed that the mutations in the 228-232 region did not introduce large changes in the overall actin structure. This suggests that residues near position 230 formed part of the tropomyosin binding site on actin in actively contracting muscle. The higher Ca(2+)-activation observed with A230Y-containing mutants can be understood in terms of a three-state model for thin filament regulation in which, in the presence of both Ca(2+) and myosin heads, the local changes of actin generated by the mutation (especially its phenolic side-chain) facilitate the transition of thin filaments from a "closed" state to an "open" state. Between 394 and 469 water molecules were identified in the different structures and it was found that actin recognizes hydrated forms of the adenine base and the Ca ion in the nucleotide binding site.
Disease
Known disease associated with this structure: Amyloidosis, Finnish type OMIM:[137350]
About this Structure
1C0G is a Protein complex structure of sequences from Dictyostelium discoideum and tetrahymena thermophila and Homo sapiens with and as ligands. Full crystallographic information is available from OCA.
Reference
Structural basis for the higher Ca(2+)-activation of the regulated actin-activated myosin ATPase observed with Dictyostelium/Tetrahymena actin chimeras., Matsuura Y, Stewart M, Kawamoto M, Kamiya N, Saeki K, Yasunaga T, Wakabayashi T, J Mol Biol. 2000 Feb 18;296(2):579-95. PMID:10669610
Page seeded by OCA on Thu Feb 21 12:01:10 2008
